The pharmacological characterization of endothelial receptor activity during the progression of atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits was examined. The data presented show that progression of atherosclerosis affects endothelial receptor functionality in different ways. Nucleotide receptor activity is preserved for longer than that of the other endothelial receptors, i.e. muscarinic- and P2y-purinoceptors. This difference means that, in WHHL rabbit aorta, some mechanisms proposed to explain impaired endothelium-mediated relaxation in atherosclerosis must be excluded. It is therefore hypothesized that atherosclerosis in genetically hyperlipidemic animals selectively influences the receptorial arrangement of endothelium, as in other published examples of selective remodeling of receptors in arteries. Endothelial cell receptors may become a new interesting target for the development of drugs to treat atheroscl